Dynamics of changes of blood inflammatory-oxidative biomarkers in acute coronary syndrome

Some inflammatory cytokines and parameters of low density lipoproteins (LDL) oxidative modification were studied in blood of 250 acute coronary syndrome (ACS) patients--Siberian inhabitants, men and women with myocardial infarction (MI) or unstable angina on first, tenth and thirtieth days of disease. The inflammatory biomarkers in men and women with MI are: increased concentrations of interleukin (IL)-6, IL-8 and C-reactive protein (CRP), especially on the first day of disease. The most significant inflammatory biomarker of ACS is increased CRP level, especially in women. Oxidative biomarkers in men with ACS are increased basal level of LDL lipid peroxidation (LPO) products and decreased LDL resistance to oxidation. Inflammatory-oxidative biomarkers IL-6, IL-8, CRP and basal level of LDL LPO products are correlated and independently associated with MI.     

Oxidative and antioxidant changes during formation of unstable atherosclerotic plaque

Oxidative and antioxidant parameters (content of LPO products and oxidized proteins, initial level of paraoxonase, content of α-tocopherol, retinol, and β-carotene) were studied at different stages of atherosclerotic foci development in coronary arteries: intact intima, lipid spot, stable young plaque, unstable plaque, stable plaque with fibrosis/calcinosis, and in various types of unstable plaques. The most typical sign of unstable plaques is high level of LPO products and low retinol content. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 500–502, November, 2007     

Procedure for determination of oxidative modification of plasma fibrinogen

The purpose of the present study was to develop a new procedure for determining the oxidative modification of plasma fibrinogen. The procedure was developed to use blood plasma from 96 males aged 35-60 years who had cardiovascular diseases: 49 patients with coronary heart disease (CHD), including 16 patients with sub-acute myocardial infarction (MI), and 47 patients with arterial hypertension without CHD. The new procedure is as follows: a rapid fibrin isolating method, a reaction with 2,4-dinitrophenylhydrazine in 2 M HCl solution, by subsequently rinsing in the ethanol : ethyl acetate (1:1) solution, dissolving the precipitate in 8 M urea, and by determining the level of the resultant dinitrophenylhydrazones by spectrophotometry at 363 nm, followed by conversion to the plasma concentration of fibrinogen. The procedure is of informative value for the degree of oxidative fibrinogen modification under oxidative stress; it is technically simple, takes little time, and shows a good reproducibility. The values of determined oxidized plasma fibrinogen by the developed procedure show a high positive correlation with the estimates of oxidized total blood protein fraction and with the values of blood lipid peroxidation. The detected elevated level of oxidized fibrinogen in CHD and MI suggests that this index is a new diagnostic marker of oxidative stress in cardiovascular diseases of atherosclerotic genesis.     

Oxidation and Endothelial Dysfunction Biomarkers of Atherosclerotic Plaque Instability. Studies of the Vascular Wall and Blood

The concentrations of LPO products (including those present in LDL), oxidative modification of proteins, paraoxonase activity, concentrations of antioxidants, lipid values and biomarkers of endothelial dysfunction were studied in the blood and coronary artery intima/media of male patients with coronary atherosclerosis without acute coronary syndrome. Blood levels of LDL oxidized apolipoproteins and lipoprotein (a) were higher, while the content of NO metabolites, sVCAM endothelial adhesion molecules, and LDL oxidation resistance were lower in men with mainly unstable atherosclerotic plaques in the coronary arteries in comparison with men with mainly stable plaques in the coronary arteries. Of these blood biomarkers, only NO metabolites, oxidized proteins, and sVCAM correlated with the presence of unstable atherosclerotic plaques. A significant correlation between the levels of biomarkers in the vascular wall and blood was detected only for LPO parameters.     

Key laboratory diagnostic biomarkers of coronary atherosclerosis

Laboratory lipid and lipoprotein biomarkers (total cholesterol - CH, triglycerides - TG, low-density and high-density lipoprotein cholesterol- LDL-CH, HDL-CH, apolipoproteins B and A1 - apoB, apoA1), carbohydrate biomarkers (plasma glucose, basal insulin), high sensitive C-reactive protein (hsCRP) and oxidative biomarkers (basal level of lipid peroxidation [LPO] products in LDL, LDL resistance to oxidation in vitro, oxidative modification of apoLDL and level of LDL lipophilic antioxidants) were studied in 388 men aged 42-70 years: 96 citizens of Western Siberia with angiographically documented coronary atherosclerosis and coronary heart disease (CHD); 292 men of population sample of citizens of Novosibirsk, including 44 men with CHD confirmed by standardized criteria and methods. Significant associations were found of coronary atherosclerosis and CHD with laboratory diagnostic biomarkers like blood levels of HDL-CH, TG, apoB, apoA1, basal insulin, hsCRP and basal level of LPO products in LDL and LDL resistance to oxidation.     

Galstena efficacy in patients with biliary dyskinesia, chronic cholecystitis and cholelithiasis]

The response of inflammation, bile secretion, lipid metabolism, LDL sensitivity to oxidation was studied in patients with bile duct dyskinesia (BDD), chronic cholecystitis (CC) and cholelithiasis (CL) before and after a course of therapy with galstena. The treatment improved general condition in 90% of the patients, dyspeptic symptoms relieved or stopped. Galstena relieved general or local inflammation, reduced mean levels of total cholesterol and LDL cholesterol, raised HDL cholesterol. In patients with BDD and cholelithiasis galstena did not change normal sensitivity of LDL to oxidation. A galstena course in BDD and CC patients significantly diminished bile lithogenicity and improved gall bladder contractility.     

Relationship between oxidized fibrinogen and hemostasis disturbances and endothelial dysfunction in myocardial infarction

Oxidative modification of fibrinogen in acute myocardial infarction increased 1.3-fold compared to that in CHD and 1.5-fold surpassed that in the control without CHD. Elevated content of oxidized fibrinogen correlated with increased levels of LPO products, von Willebrand factor, and fibrin degradation products, with accelerated leukocyte and platelet aggregation, and reduced content of NO metabolites in the plasma. Independent associations of oxidized fibrinogen with myocardial infarction and typical thrombogenic and hypercoagulation hemostasis disorders and endothelial dysfunctions were revealed. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 389–391, April, 2008     

Antioxidant and endothelium-stabilizing effects of simvaglyzin on rabbits with experimental hypercholesterolemia

Simvaglyzin, a complex compound of simvastatin and glycyrrhizic acid, administered to rabbits with experimental hypercholesterolemiain in doses equivalent to 66.6 and 40 μg/kg simvastatin exhibited antioxidant capacity (decreased the content of lipid peroxidation products in the blood by 27–41%) and endothelium-normalizing effect (decreased the level of von Willebrand factor and endothelin-1 by 26–58 and 21–29%, respectively, compared to 200 μg/kg simvastatin, p<0.05). Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 8, pp. 171–174, August, 2008     

Inhibition of low density lipoprotein oxidation by melatonin

The antioxidant activity of the lipophilic hormone melatonin, “an ideal inhibitor of free radicals,” is studied in models of cellular (peritoneal mouse macrophages) and copper-induced oxidation of low density lipoproteins. Oxidative modification of low density lipoproteins is assessed by accumulation of thiobarbituric acid reactive substances and degradation of¹²⁵I-labeled lipoproteins in a fresh culture of macrophages. Melatonin inhibits in a dose-dependent manner cellular and copper-induced oxidation of lipoproteins and production of the superoxide anion radical by macrophages, the mean concentrations of 50% inhibition being 300, 1230, and 900 μM, respectively. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 399–402, October, 1996     

Study of cholesterol-lowering effect and safety of simvaglisin on rabbit model of hypercholesterolemia

Using rabbit model of experimental hypercholesterolemia we showed that the hypocholesterolemic effect of simvaglisin, a complex preparation containing simvastatin and glycyrrhizic acid, in doses corresponding to 40, 66.5, and 100 mg/kg/day simvastatin is equal to the hypocholesterolemic effect of 200 mg/kg/day simvastatin alone. The total blood cholesterol decreased by 39, 36, 47, and 38% (p<0.05), respectively, after 20-day course of the preparation. Myotoxicity of simvaglisin evaluated by serum creatine phosphokinase was lower than that of simvastatin. After 30-day treatment, this parameter was lower by 26, 24, and 29% (p<0.05) than the corresponding parameter for simvastatin. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 285–287, March, 2008